RATIONALE: Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some find cancer cells and help kill them or carry cancer-killing substances to them. Others interfere with the ability of cancer cells to grow and spread. Drugs used in chemotherapy, such as bendamustine hydrochloride, also work in different ways to kill cancer cells or stop them from dividing. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Lenalidomide may stop the growth of mantle cell lymphoma by blocking blood flow to the cancer. It is not yet known whether giving rituximab together with bendamustine and bortezomib is more effective than rituximab and bendamustine, followed by rituximab alone or with lenalidomide in treating mantle cell lymphoma.

Patients receive induction therapy comprising rituximab IV on day 1 and bendamustine hydrochloride IV over 60 minutes on days 1-2. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then proceed to arm E.

Biological: rituximab

Given IV

Drug: bendamustine hydrochloride

Given IV

Experimental: Arm B

Patients receive induction therapy comprising bortezomib IV subcutaneously (SC) on days 1, 4, 8, and 11 and rituximab and bendamustine hydrochloride as patients in arm A. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then proceed to arm F.

Patients receive bortezomib, rituximab, and bendamustine hydrochloride as patients in arm B. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then proceed to arm H.

Biological: rituximab

Given IV

Drug: bendamustine hydrochloride

Given IV

Drug: bortezomib

Given IV or SC

Drug: lenalidomide

Given PO

Experimental: Arm E

Patients receive consolidation therapy comprising rituximab IV on day 1. Courses repeat every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.

Biological: rituximab

Given IV

Experimental: Arm F

Patients receive consolidation therapy comprising rituximab IV on day 1. Courses repeat every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.

Biological: rituximab

Given IV

Experimental: Arm G

Patients receive consolidation therapy comprising lenalidomide orally (PO) daily on days 1-21 every 4 weeks and rituximab IV every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.

Biological: rituximab

Given IV

Drug: lenalidomide

Given PO

Experimental: Arm H

Patients receive consolidation therapy comprising lenalidomide PO daily on days 1-21 every 4 weeks and rituximab IV every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.

Women of childbearing potential and sexually active males use an accepted and effective method of contraception

Men must agree to use a latex condom during sexual contact with a female of child-bearing potential, even if they have had a successful vasectomy

All patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure

No evidence of prior malignancy except adequately treated non-melanoma skin cancer, in situ cervical carcinoma, or any surgically or radiation-cured malignancy continuously disease free for ≥ 5 years so as not to interfere with interpretation of radiographic response

Patient agrees that if randomized to Arms C or D, and proceed onto Arms G or H, they must register into the mandatory RevAssist® program, and be willing and able to comply with the requirements of RevAssist®

Patients must have no medical contra-indications to, and be willing to take, deep vein thrombosis (DVT) prophylaxis as all patients registering to the lenalidomide/rituximab Arms G and H will be required to have DVT prophylaxis

Patients randomized to Arms G or H who have a history of a thrombotic vascular event will be required to have therapeutic doses of low-molecular weight heparin or warfarin to maintain an INR between 2.0 - 3.0

Patients on Arms G and H without a history of a thromboembolic event are required to take a daily aspirin (81 mg or 325 mg) for DVT prophylaxis

Women must agree to abstain from donating blood during study participation and for at least 28 days after discontinuation from protocol treatment

Males must agree to abstain from donating blood, semen, or sperm during study participation and for at least 28 days after discontinuation from protocol treatment

HIV-positive patients are not excluded but, to enroll, must meet all of the below criteria:

HIV is sensitive to antiretroviral therapy

Must be willing to take effective antiretroviral therapy, if indicated

No history of CD4 prior to or at the time of lymphoma diagnosis < 300 cells/mm³

No history of AIDS-defining conditions

If on antiretroviral therapy, must not be taking zidovudine or stavudine

Must be willing to take prophylaxis for Pneumocystis jiroveci pneumonia (PCP) during therapy and until at least 2 months following the completion of therapy or until the CD4 cells recover to over 250 cells/mm³, whichever occurs later

Patients must not have hypersensitivity to bortezomib, boron, or mannitol

Patients must not have a serious medical or psychiatric illness likely to interfere with study participation

PRIOR CONCURRENT THERAPY:

No prior therapy for MCL, except < 1 week of steroid therapy for symptom control

HIV-positive patients are not excluded, but to enroll, must meet all of the below criteria:

Must be willing to take effective antiretroviral therapy if indicated

If on antiretroviral therapy, must not be taking zidovudine or stavudine

Patients must not be participating in any other clinical trial or taking any other experimental medications within 14 days prior to registration

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01415752